Method for Treating Pervasive Development Disorders

ABSTRACT

A method of utilizing the chymotrypsin level of an individual as a measure of the success of secretin, other neuropeptides, and peptides or digestive enzyme administration to such individuals, and in particular, as a prognosticative of potential secretin, other neuropeptides, peptides, and digestive enzyme administration for persons having ADD, ADHD, Autism and other PDD related disorders.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. application Ser.No. 12/283,090, filed Sep. 8, 2008, which is a continuation of U.S.application Ser. No. 10/681,018, filed Oct. 8, 2003, which is acontinuation of U.S. application Ser. No. 09/707,395, filed Nov. 7,2000, which is a continuation-in-part of U.S. application Ser. No.09/466,559, filed Dec. 17, 1999. Each of these applications are hereinincorporated in their entirety by reference.

BACKGROUND

1. Technical Field

The present invention relates generally to a method for treatingindividuals diagnosed with a form of PDD (pervasive developmentdisorder) and other disorders such as ADD (attention deficit disorder)and ADHD (attention deficit hyperactivity disorder). More specifically,the present invention is directed to therapeutic method for treatingindividuals with such disorders by administering secretin, otherneuropeptides, peptides, and/or digestive enzymes, as well as aprognosticative method for determining the potential effectiveness ofthe administration of secretin, other neuropeptides, peptides, and/ordigestive enzymes for the treatment of such disorders.

2. Description of Related Art

PDDs are a class of disorders defined by both American and Internationaldiagnostic systems (i.e., the Diagnostic and Statistical Manual ofMental Disorders, 4th edition (DSM-IV) and World Health Organization:International Classification of Diseases, Tenth revision (ICD-10)). Thespectrum of PDDs include disorders such as Autism, Aspergers, ADD, andADHD. PDDs are typically characterized by multiple distortions in thedevelopment of basic psychological functions that are involved in thedevelopment of social skills and language, such as attention, perceptionreality testing and motor movement. In addition, many children diagnosedwith Autism, for example, suffer from primary diffuse gastrointestinalproblems such as protracted diarrhea and constipation. Although PDDs arecurrently of unknown etiology, many conventional methods, such asdietary alteration, behavioral modification, and medication, have beenutilized for treating individuals suffering from PDD related disorders.Unfortunately, PDD related disorders have no known treatment beyond thatwhich is symptomatic, and these conventional methods have provenunsuccessful in allowing such children and adults to become symptom, ordisorder free.

A child which displays signs of developmentally inappropriateinattention, impulsivity and hyperactivity is typically diagnosed ashaving ADD and/or ADHD. With these disorders, there can be markeddisturbances of organization, distractibility, impulsivity,restlessness, and other disturbances of language and/or social behavior.A combination of psychiatric care and medicine is typically used fortreating children with ADD and ADHD.

It was recently discovered that the administration of secretin, agastrointestinal peptide hormone, to children diagnosed with Autismresulted in ameliorating the symptoms associated with Autism. Thisfinding was published in the article by Horvath et al., entitledImproved Social and Language Skills After Secretin Administration InPatients with Autistic Spectrum Disorders, Journal of the Associationfor Academic Minority Physician Vol. 9 No. 1, pp. 9-15, January, 1998.The secretin administration, as described in Horvath, was performed as adiagnostic procedure, i.e., to stimulate pancreaticaobiliary secretionduring an upper gastrointestinal endoscopy, rather than as a therapeuticprocedure. Although the specific mechanism by which the secretinimproved the autistic-related symptoms was not specifically identified,Horvath postulated that secretin may have had a direct or indirecteffect on the central nervous system. What is important, however, isthat this was the first time that gastrointestinal problems of autisticchildren were linked to a possible etiology in Autism.

Accordingly, in view of such findings, a method for determining whetheran individual suffering from a disorder in the PDD spectrum will benefitfrom the administration of secretin, other neuropeptides, peptidesand/or digestive enzymes, as well as a therapeutic method for treatingsuch individuals with the administration of secretin, otherneuropeptides, peptides and/or digestive enzymes, are highly desired.

SUMMARY OF THE INVENTION

The present invention is directed to a method of analyzing thechymotrypsin level of an individual to determine the potential benefitof the administration of secretin, other neuropeptides, peptides and/ordigestive enzyme administration to such individual, and in particular,as a prognosticative of potential secretin, other neuropeptides,peptides, and/or digestive enzyme administration for individualsdiagnosed as having ADD, ADHD, Autism and other PDD related disorders.

In one aspect, a method for determining the efficacy of secretin, otherneuropeptides, peptides, or digestive enzymes for the treatment of anindividual diagnosed with a pervasive developmental disorder (PDD)comprises obtaining a sample of feces from an individual, determining aquantitative level of chymotrypsin present in the sample, andcorrelating the quantitative level of chymotrypsin determined to bepresent in the sample with the PDD to determine the efficacy of treatingthe individual with secretin, other neuropeptides, peptides, ordigestive enzyme administration.

In another aspect, a therapeutic method for treating an individualdiagnosed with a PDD pervasive developmental disorder comprisesdetermining the efficacy of the administration of secretin, otherneuropeptides, peptides, and digestive enzyme for the treatment of theindividual based on a measure of the individual's chymotrypsin level,and administering secretin, other neuropeptides, peptides, or digestiveenzymes to the individual based on the determination of the measure ofthe individual's chymotrypsin level.

The present invention involves determining the presence of abnormalprotein digestion of individuals, especially children, by measuring thechymotrypsin levels so as to determine if the individual is likely tobenefit from the administration of secretin, digestive enzymes, peptidesand/or neuropeptides. Although there have been methods to test fecalsamples for indications of cystic fibrosis and pancreatic diseases ininfants, none of the known methods have tested fecal samples indetermining the benefits of administering secretin, other neuropeptides,peptides and/or digestive enzymes to individuals suffering from a PDD.Indeed, in so far as an individual's fecal chymotrypsin level is a broadmeasure of protein and fat digestion, such levels can be applied to allthose who may benefit from improvements in this mode of digestion.Furthermore, as low measures of fecal chymotrypsin expresses anabnormality of protein digestion, it is postulated that an improvementof protein digestion to promote normal growth and development of anindividual suffering from a PDD by the administration of secretin, otherneuropeptides, peptides and/or digestive enzymes, can ameliorate thesymptomatologies of PDDs.

Accordingly, in another aspect of the present invention, a therapeuticmethod is provided for treating an individual diagnosed with a PDDincluding but not limited to Autism, Aspergers, ADD and ADHD, comprisingthe steps of:

determining the effectiveness of secretin administration for thetreatment of the individual based on a measure of the individual'schymotrypsin level; and

administering secretin therapy to the individual based on thedetermination of the measure of the individuals chymotrypsin level.

In yet another aspect, the therapeutic method involves administering afecal chymotrypsin test to measure an individual's fecal chymotrypsinlevel. Preferably, an enzymatic spectrophotometry method is used formeasuring the fecal chymotrypsin level of the individual. Upondeterminating that an individual has an abnormal level of chymotrypsin,the individual is preferably administered 1 U/kg of body weight ofporcine or human secretin by means of an intravenous push method. Thismethod can be described as the administration of an IV push of salinesolution and secretin to equal 1 U/kg of body weight. The individualthen receives 1 unit test dose (absolute). A period of one minute isallowed to pass to determine if the individual has any allergicreactions to the secretin. After one minute has elapsed, if nourticarial reaction or any other allergic reaction has occurred, theremainder of the dose is administered. Subsequent fecal chymotrypsinsamples are then gathered at one week intervals post administration todetermine any changes in the chymotrypsin levels.

These and other aspects, features and advantages of the presentinvention will be described and become apparent from the followingdetailed description of preferred embodiments, which is to be read inconnection with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates the overall net change in results of a CARS test(Childhood Autism Rating Scale) depicting behavior of 16 autisticchildren pre-secretin and post-secretin administration, where the solidlines indicate pre-secretin scores and the dotted lines indicatepost-secretin scores;

FIG. 2 illustrates percentage change from pre-secretin to post-secretinadministration in the average scores of the respective components of theCARS test of FIG. 1;

FIG. 3 illustrates the change in CARS scores for the sub-class Visualresponse from pre-secretin administration to three weeks post-secretinadministration, where the solid lines indicate pre-secretin scores andthe dotted lines indicate post-secretin scores;

FIG. 4 illustrates the change in CARS scores for the sub-class VerbalSkills from pre-secretin administration to three weeks post-secretinadministration, where the solid lines indicate pre-secretin scores andthe dotted lines indicate post-secretin scores;

FIG. 5 illustrates the change in CARS scores for the sub-classTouch/Taste/Smell from pre-secretin administration to three weekspost-secretin administration, where the solid lines indicatepre-secretin scores and the dotted lines indicate post-secretin scores;

FIG. 6 illustrates the change in CARS scores for the sub-class ObjectUse from pre-secretin administration to three weeks post-secretinadministration, where the solid lines indicate pre-secretin scores andthe dotted lines indicate post-secretin scores;

FIG. 7 illustrates the change in CARS scores for the sub-class Listeningfrom pre-secretin administration to three weeks post-secretinadministration, where the solid lines indicate pre-secretin scores andthe dotted lines indicate post-secretin scores;

FIG. 8 illustrates the change in CARS scores for the sub-class Imitationfrom pre-secretin administration to three weeks post-secretinadministration, where the solid lines indicate pre-secretin scores andthe dotted lines indicate post-secretin scores;

FIG. 9 illustrates the change in CARS scores for the sub-class Body Usefrom pre-secretin administration to three weeks post-secretinadministration, where the solid lines indicate pre-secretin scores andthe dotted lines indicate post-secretin scores;

FIG. 10 illustrates the change in CARS scores for the sub-classAdaptation to Change from pre-secretin administration to three weekspost-secretin administration, where the solid lines indicatepre-secretin scores and the dotted lines indicate post-secretin scores;

FIG. 11 illustrates the change in CARS scores for the sub-class ActivityLevel from pre-secretin administration to three weeks post-secretinadministration, where the solid lines indicate pre-secretin scores andthe dotted lines indicate post-secretin scores;

FIG. 12 illustrates the change in CARS scores for the sub-class GeneralImpression from pre-secretin administration to three weeks post-secretinadministration, where the solid lines indicate pre-secretin scores andthe dotted lines indicate post-secretin scores;

FIG. 13 illustrates the measured fecal chymotrypsin levels of 16autistic children pre-secretin administration;

FIG. 14 illustrates the measured fecal chymotrypsin levels of the 16autistic children approximately one week post-secretin administration;

FIG. 15 illustrates the measured fecal chymotrypsin levels of 28 ADDchildren;

FIG. 16 illustrates the measured fecal chymotrypsin levels of 34 ADHDchildren; and

FIG. 17 illustrates Ritalin levels administered before and aftersecretin administration in five of the ADHD children in FIG. 16, wherethe shaded bars indication pre-secretin Ritalin levels and thenon-shaded bars indicate post-secretin Ritalin levels.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The present invention is directed to a method of analyzing chymotrypsinlevels in persons, especially children, as a measure of the success ofadministering secretin, other neuropeptides, peptides and/or digestiveenzymes for the therapeutic treatment of ADD, ADHD, Autism, Aspergersand other PDD related disorders. The use of secretin for the treatmentof Autism is presently in the investigational stages. When the positiveaffects of the neuropeptide secretin on childhood autism Were firstdiscovered and published, research was conducted by the present inventorto formulate a process that would enable one to definitively determineif individuals, especially children, having a PDD could be tested priorto the administration of secretin for its possible efficacy for treatingPDD. Tests were performed to measure the fecal chymotrypsin levels(referred to herein as Fecal Chymotrypsin Test) in children who span theentire PDD spectrum and whose symptomotology place them in this DSM IVcategory. As demonstrated below, such tests revealed that a majority ofthe children diagnosed with autism, ADD and ADHD, for example, hadabnormal chymotrypsin levels. It is believed that such abnormal levelsof chymotrypsin have not heretofore been identified in the PDDpopulation of children and adults.

It is postulated that the abnormal levels of chymotrypsin are due to theinability of the pancreas to release bicarbonate ions, due to the lackof secretin mechanization in the small intestines. The small intestinehas a pH in the range of 1.0-1.5 when the bolus of food enters the smallintestines. Normally, plasma concentrations of secretin increase whenthe duodenal pH is below 4.5, and typically doubles during thepostprandial period. The s cells in the proximal portion of the smallintestines release secretin in response to this low pH. The secretin isthen released into the bloodstream and ultimately reaches the pancreas.In response, the pancreas releases bicarbonate ions, water andelectrolytes into the small intestines thus neutralizing the pH bybringing it from a 1.0-1.5 to approximately 6.5.

Following this, the pancreas secretes the enzyme trypsin in an inactiveform trypsinogen. The trypsinogen is converted to trypsin in the smallintestines. In an environment where the pH is 6.5 or greater, thetrypsin catalyzes the formation of chymotrypsinogen to chymotrypsin.These enzymes are essential for the digestion of protein. In the absenceof protein digestion, the amino acids necessary for the growth anddevelopment of individuals are absent. Therefore, based on testsperformed by the present inventor, it is postulated that the increase ofprotein digestion of an individual suffering from PDD can lead to theimprovement of such disorders. Accordingly, since secretin isresponsible for aiding in the protein digestion process, it has beendetermined that the presence of abnormal protein digestion inindividuals, especially children, is indicative of which individuals arelikely to benefit from the administration of secretin.

Indeed, in accordance with the present invention, experimental resultshave shown that the potential benefit of administering secretin, otherneuropeptides, peptides and/or digestive enzymes to individualsdiagnosed with developmental disorders falling within the entirespectrum of PDD may be predetermined by analyzing the measured fecalchymotrypsin levels of such individuals. More specifically, asillustrated below, it has been determined that sub-normal to abnormallevels of fecal chymotrypsin in children/adults with PDD symptoms willbenefit from the administration of secretin, other neuropeptides,peptides and/or digestive enzymes. In addition, experimental tests bythe present inventor have revealed that the administration of secretin,other neuropeptides, peptides and/or digestive enzymes to others beyondthose of who are autistic, especially those diagnosed with ADD and ADHDwill benefit from the administration of secretin, other neuropeptides,peptides and/or digestive enzymes.

The following experiments describe exemplary diagnosis and treatmentprocedures in accordance with the invention. It is to be understood thatthese experiments and corresponding results are set forth by way ofillustration only, and nothing therein shall be construed as alimitation on the overall scope of the invention.

I. Experiment 1

In this experiment, 16 children diagnosed as having autism wereadministered the following Fecal Chymotrypsin Test in accordance with anembodiment of the invention. First, approximately 2 grams of stool werecollected from each child and placed in a sterile container (although itis to be understood that any quantity of stool may be collected, as 2grams of stool is not a required amount). Each stool sample was thenanalyzed using, e.g., an enzymatic photospectrometry analysis as isknown by those skilled in the art, to determine the level of fecalchymotrypsin in the stool. Although the enzymatic photospectrophotometryprocess is preferred, any suitable conventional method may be used formeasuring the fecal chymotrypsin levels. The measured chymotrypsinlevels of the 16 autistic children are illustrated in FIG. 13.

After determining the chymotrypsin levels of the stools, each of theselevels were compared with threshold chymotrypsin levels to determine ifthe child was likely to benefit from secretin administration. By way ofexample, with the fecal chymotrypsin tests of the stool samples beingperformed at 30° C., normal levels of chymotrypsin are deemed to lieabove 8.4 U/gram, whereas pathologically abnormal levels are deemed tolie below 4.2 U/gram. In addition, chymotrypsin levels between 8.4U/gram and 4.2 U/gram are considered equivocal, and further testing ofthe individual's fecal chymotrypsin levels over a period of time shouldbe performed. It is to be noted that as shown in FIG. 13, all of the 16autistic children that were tested had abnormal levels of fecalchymotrypsin pre-secretin administration.

Another stool sample was then collected from each child two days afterthe first test and analyzed to determine the chymotrypsin levels. Thissecond test is preferably performed to obtain additional chymotrypsinmeasurements to make a more accurate determination. Those childrenhaving abnormal levels of chymotrypsin in their stools are consideredcandidates for secretin administration. Other factors that may beconsidered in determining which children are potential candidates forsecretin administration aside from the fecal chymotrypsin levels includea previously diagnosed history of autism, a history of gastrointestinal(GI) dysfunction, including any history of protracted diarrhea orconstipation lasting for a weeks or months, as well as a self-limitingdiet consisting primarily of carbohydrates.

Upon determining that a given child was likely to benefit from secretinadministration based on the results of the fecal chymotrypsin test, thechild was administered a CARS (Childhood Autism Rating Scale) test priorto being scheduled for secretin infusion.

For each of the 16 autistic children tested, a preferred secretininfusion process according to the present invention was performedinvolving the administering of 1 U/kg of body weight of Secretin-Ferringfor a period of nine months at intervals of approximately 6 weeks. Inaddition, another CARS test was administered to each of the 16 autisticchildren 3 weeks post secretin administration to determine if theirautism had changed post infusion.

A preferred secretin infusion process includes the initial step ofprepping an arm of the candidate child with an IV injection of saline. Atest dose of 1 U of Secretin-Ferring is then administered to the child.Approximately one minute after infusion, the child is examined for signsof allergic reaction including rash, increased heart rate, and increaseof blood pressure. If the child does not display any signs of allergicreaction, the remaining units of Secretin-Ferring is administered to thechild in the manner of an IV push, which is then followed by a salineflush. Subsequently, each child receives a 1 U/kg of body weightinfusion of Secretin-Ferring approximately every 6 weeks for 9 months.It is to be understood that any commercially available form of secretinmay be used.

Results of Experiment 1

The results of Experiment 1 are illustrated in FIGS. 1-14. For instance,approximately one week after the first secretin infusion, the fecalchymotrypsin level of each of the 16 autistic children was measuredagain. The results of this test are illustrated in FIG. 14. As shown,the chymotrypsin level of each of the 16 autistic children testincreased post-secretin administration (as compared with the levelsshown in FIG. 13).

In addition, FIG. 1 illustrates the pre-secretin CARS test results(solid line) and the post-secretin CARS test results (dotted line) foreach of the 16 autistic children tested approximately 3 weeks after thefirst secretin administration. Most notably, FIG. 1 illustrates anoverall decrease in the CARS scores indicating improvements in thePDD/autistic symptoms of the children. In particular, FIG. 2 illustratesrespective percentage decreases in components of CARS scores, whereinthe numbers represent percentage change in the average of the scores ineach component of the CARS test post-secretin administration. Inparticular, FIGS. 3-12 illustrate the improved scores of each of the 16autistic children for the individual components of the CARS scores. Asshown, the component scores demonstrated improvement except for the fearcomponent which increased 3 weeks post infusion.

II. Experiment 2

In this experiment, 37 autistic children with abnormal fecalchymotrypsin levels were administered secretin over the course of 6months using the secretin infusion process described above. Their fecalchymotrypsin (FC) levels were measured weekly using the fecalchymotrypsin test described above.

Results of Experiment 2

Out of the 37 autistic children tested, the fecal chymotrypsin levels of34 children had returned to normal after 6 months, the fecalchymotrypsin levels of 2 children moved to equivocal, and the fecalchymotrypsin level of 1 child remained abnormal. These results of thisexperiment are listed in the following Table 1.

TABLE 1 6 Months Post- Pre-Secretin Secretin Autistic Children TestedAdministration Administration # Autistic Children w/Abnormal 37 1 FClevels # Autistic Children w/Equivocal 0 2 FC levels # Autistic Childrenw/normal 0 34 FC levels

III. Experiment 3

In this experiment, the fecal chymotrypsin levels of 28 childrendiagnosed with ADD were obtained using the fecal chymotrypsin testdescribed above in Experiment 1. FIG. 15 illustrates the measured fecalchymotrypsin levels of these 28 children. It is to be noted that, asshown in FIG. 15, all of the 28 ADD children were found to havesub-normal fecal chymotrypsin levels since all of the values fell below8.4 U/g. More specifically, 8 out of 28 children were determined to havean equivocal fecal chymotrypsin level and 20 out of the 28 children weredetermined to have a pathologic level of fecal chymotrypsin. As notedabove, a chymotrypsin level of 8.4 U/g is considered a reference valuefor normal levels of chymotrypsin.

Of these 28 children who were diagnosed with ADD and abnormal fecalchymotrypsin levels, 10 were administered digestive enzymes comprisingamylase, proteases, lipases, sucrase, maltase, and other digestiveenzymes. These digestive enzymes were administered one tablet at eachmealtime (i.e., three times a day), adjusted for the age and weight ofthe child. More specifically, for the ADD children ages 1-6, a quantityof digestive enzymes of approximately 4,000-8,000 U.S.P. Units/tabletcomprising lipase, amylase and protease were administered. For the ADDchildren of ages 7-12, a quantity of digestive enzymes of approximately8,000-12,000 U.S.P. Units/tablet comprising lipase, amylase and proteasewere administered. Other digestive enzymes that were administered insmaller quantities included cellulase, sucrase and maltase. Thesedigestive enzymes were administered over a period of 6 months.

Results of Experiment 3

At the time of this experiment, 4 out of the 10 children who wereadministered the digestive enzymes were taking Ritalin. As is known inthe art, Ritalin is a stimulant medication used to treat children andadults with ADD and ADHD. More specifically, it is used to treathyperactivity and attention problems. As a result of the administrationof the digestive enzymes, all of the 4 children who had been takingRitalin were able to completely stop taking the Ritalin. In addition,significant improvements in the behavior of the other 6 children werenoted. These results are shown in the following Table 2:

TABLE 2 # ADD Children w/Sub-normal FC levels 28 # of the 28 ADDChildren With Abnormal FC levels That 10 Were Administered DigestiveEnzymes # of the 10 ADD Children That Were Administered Digestive 4Enzymes Who Were Taking Ritalin # ADD Children Requiring RitalinAdministration 6 months 0 Post Administration of Digestive Enzymes

IV. Experiment 4

In this experiment, the fecal chymotrypsin levels of 34 childrendiagnosed with ADHD were obtained using the fecal chymotrypsin testdescribed above in Experiment 1, the levels of which are illustrated inFIG. 16. As shown, 32 children out of 34 children tested were determinedto have sub-normal fecal chymotrypsin levels. It is to be further notedthat 24 of the 34 children were found to have pathologic levels of fecalchymotrypsin.

To determine the effect of secretin administration on ADHD children, 5of the 24 children having a pathologic fecal chymotrypsin level wereadministered secretin using the secretin infusion process describedabove.

Results of Experiment 4

The results of this experiment are set forth in FIG. 17, whichillustrates the required levels of Ritalin (in mg) of the 5 childrentested both pre-secretin administration (as indicated by the shadedbars) and 6 months post-secretin administration (as indicated by thenon-shaded bars). It is to be appreciated that as shown in FIG. 17, eachof the 5 children who were administered secretin demonstratedsignificant changes post-secretin administration with respect to thelevel of Ritalin (mg) that each child needed to remain at the samefunctional level as their functional level prior to secretinadministration.

V. Experiment 5

In this experiment, to determine the effect of the administration ofdigestive enzymes to ADHD children, 9 children of the 34 childrendiagnosed with ADHD (in experiment 4 described above) whose fecalchymotrypsin levels were determined to be pathologic were administereddigestive enzymes. Such digestive enzymes included amylase, lipase,proteases, sucrases, maltase, and other digestive enzymes. Each childwas administered 1 tablet of digestive enzymes at each mealtime (i.e.,three times a day), adjusted for age and weight of the child. Morespecifically, for the ADHD children ages 1-6, a quantity of digestiveenzymes of approximately 4,000-8,000 U.S.P. Units/tablet comprisinglipase, amylase and protease were administered. For the ADHD children ofages 7-12, a quantity of digestive enzymes of approximately 8,000-12,000U.S.P. Units/tablet comprising lipase, amylase and protease wereadministered. Other digestive enzymes that were administered in smallerquantities included cellulase, sucrase and maltase. The digestiveenzymes were administered over a 6 month period.

Results of Experiment 5

It is to be appreciated that as a result of the administration ofdigestive enzymes over the 6 month period, all 9 children were able toreduce their required Ritalin levels. Most notably, 2 of the 9 childrenwere able to stop taking Ritalin after 6 months of digestive enzymeadministration. The results of experiment 5 are illustrated in thefollowing Table 3:

TABLE 3 # ADHD Children w/Abnormal FC levels Who Were 9 AdministeredDigestive Enzymes # Of The 9 ADHD Children Whose Ritalin Levels Were 9Reduced 6 months Post-Digestive Enzyme Administration # Of The 9 ADHDChildren Who Stopped Taking Ritalin 2 6 Months Post-Digestive EnzymeAdministration

VI. Experiment 6

The following experiment was performed to determine the effect of theadministration of digestive enzymes to Autistic children. In thisexperiment, the fecal chymotrypsin levels of 17 autistic children ofvarying ages were measured (pre-digestive enzyme administration) usingthe method described above in Experiment 1. In addition, the fecalchymotrypsin levels of these 17 children were measured 6 months postdigestive enzyme administration after receiving digestive enzyme therapyas described below. The following table demonstrates the measured fecalchymotrypsin levels of these 17 children:

TABLE 4 Pre-DE Administration 6-Months Post-DE Fecal AdministrationPatient Age Chymotrypsin Levels Fecal Chymotrypsin Levels 1 2.5 3.3 7.12 7 1.5 3.8 3 9 4.0 7.8 4 3.5 2.0 10.2 5 5 3.3 8.0 6 4 1.0 6.8 7 8 1.610.2 8 6 4.0 12.2 9 7 6.8 14.9 10 3 2.8 6.2 11 5 3.4 not available 12 32.0 4.0 13 2 4.0 4.6 14 11 3.3 5.0 15 9 2.2 9.2 16 8 1.4 12.0 17 7 3.86.0

As illustrated, each of the 17 autistic children were found to haveeither su-normal or pathologic fecal chymotrypsin levels. In particular,the fecal chymotrypsin level of patient #9 was found to be sub-normal asit fell below 8.4 U/g and the fecal chymotrypsin levels of the remaining16 children were found to be pathologic since the levels fell below 4.2U/g.

Each of the 17 autistic children were administered digestive/pancreaticenzymes comprising amylases, proteases, lipases, sucrases, maltases, andother digestive/pancreatic enzymes including trypsin and chymotrypsin.The digestive enzymes were administered on a daily basis at eachmealtime, preferably 3-6 times per day. The quantity of digestiveenzymes were adjusted for the weight and ages of the child. Forinstance, depending on the weight and age of the child, a preferredquantity of lipases ranges from 4,000-20,000 U.S.P., a preferredquantity of proteases ranges from 10,000-50,000 U.S.P., a preferredquantity of amylases ranges from 10,000-60,000 U.S.P., a preferredquantity of pancreatin (pancreatic extract) ranges from 2,000-6,000U.S.P., a preferred quantity of chymotrypsin ranges from 2-5 mg and apreferred quantity of trypsin ranges from 60-100 mg. In addition, anycombination of two or more types of any of the above digestive enzymesmay be administered.

Results of Experiment 6

As illustrated in Table 4, the measured fecal chymotrypsin levels of atleast 16 of the 17 autistic children were found to increase 6 monthspost-digestive enzyme administration. Most notably, the fecalchymotrypsin levels of 5 children (patients #4, 7, 8, 15, and 16) thatwere initially found to be pathologic had increased to the normal range6 months post-digestive enzyme administration.

Furthermore, a notable decrease in autistic symptomotology of each ofthe 17 autistic children was observed as a result ofdigestive/pancreatic enzyme administration. These observations areoutlined in the following tables. Table 5 outlines the responses thatwere reported after administration of digestive enzymes to the autisticchildren in the range of ages 2-4 (i.e., 6 of the 17 children listed inTable 4). Each numeric entry in Table 5 indicates the number of children(of the 6 children ages 2-4) exhibiting the corresponding behavior.

TABLE 5 3 Months 6 Months Behavior Pre-DE Post-DE Post-DE some eyecontact 0 2 5 toilet trained 1 2 3 some toilet training 2 3 notavailable (not included above) some speech 2 3 6 formed bowel movement 12 6 hyperactive 5 3 1 plays with others 0 2 4 hand flapping 4 2 1

Furthermore, Table 6 outlines the responses that were reported afteradministration of digestive enzymes the autistic children of ages 5-12(i.e., 11 of the 17 children listed in Table 4). Again, each numericentry in Table 6 indicates the number of children (of the 11 childrenages 5-12) exhibiting the corresponding behavior.

TABLE 6 3 Months 6 Months Behavior Pre-DE Post-DE Post-DE some eyecontact 8 6 8 toilet trained 3 6 6 some toilet training 2 not available4 (not included above) some speech 6 8 10 formed bowel movement 2 7 10hyperactive 9 5 3 plays with others 3 5 8 hand flapping 6 5 1

In summary, the results of the experiments described herein demonstratethat the fecal chymotrypsin level of an individual having one or moredevelopmental disorders falling within the spectrum of PDD can be usedas a marker to determine the benefit of administering secretin, otherneuropeptides, peptides and/or digestive enzymes to the individual.Indeed, the above experiments indicate that the administration ofsecretin, other neuropeptides, peptides and/or digestive enzymes tochildren suffering from a disorder such as autism, ADD and ADHD, forexample, and having sub-normal to pathologic levels of fecalchymotrypsin, will result in the amelioration of symptomatologies ofsuch disorders.

Although illustrative embodiments have been described herein withreference to the accompanying drawings, it is to be understood that thepresent invention is not limited to those precise embodiments, and thatvarious other changes and modifications may be affected therein by oneskilled in the art without departing from the scope or spirit of theinvention. All such changes and modifications are intended to beincluded within the scope of the invention as defined by the appendedclaims.

1-86. (canceled)
 87. A pharmaceutical composition comprising pancreaticenzymes, wherein said pancreatic enzymes comprise approximately 12,000to approximately 24,000 U.S.P. units of an amylase, protease or lipase.88. A composition comprising pancreatic enzymes, wherein said pancreaticenzymes comprise approximately 24,000 to approximately 36,000 U.S.P.units of a amylase, protease or lipase.
 89. A composition comprisingpancreatic enzymes, wherein said pancreatic enzymes comprises fromapproximately 4000 to approximately 20,000 U.S.P. units of lipases; fromapproximately 10,000 to approximately 50,000 U.S.P units of proteases;or from approximately 10,000 to approximately 60,000 U.S.P. units ofamylases.
 90. The composition of claims 87-89, wherein saidpharmaceutical composition is provided as a tablet.
 91. A method oftreating one or more symptoms of a condition associated with abnormalpancreatic function in a patient, comprising: administering to saidpatient a pharmaceutical composition comprising pancreatic enzymes,wherein said pancreatic enzymes comprise approximately 12,000 toapproximately 24,000 U.S.P. units of a amylase, protease or lipase. 92.A method of treating one or more symptoms of a condition associated withabnormal pancreatic function in a patient, comprising: administering tosaid patient a pharmaceutical composition comprising pancreatic enzymes,wherein said pancreatic enzymes comprise approximately 24,000 toapproximately 36,000 U.S.P. units of an amylase, protease or lipase. 93.A method of treating one or more symptoms of a condition associated withabnormal pancreatic function in a patient, comprising: administering tosaid patient a pharmaceutical composition comprising pancreatic enzymes,wherein said pancreatic enzymes comprises from approximately 4000 toapproximately 20,000 U.S.P. units of lipases; from approximately 10,000to approximately 50,000 U.S.P units of proteases; or from approximately10,000 to approximately 60,000 U.S.P. units of amylases.
 94. The methodof claims 92-94, wherein said pharmaceutical composition is provided asa tablet.
 95. A method of treating a pervasive development disorder(PDD), comprising: (a) obtaining a fecal sample from the individual; (b)measuring a level of chymotrypsin present in the fecal sample; (c)identifying the individual as likely to benefit from administration ofthe pharmaceutical composition if the measured fecal chymotrypsin levelis sub-normal and the individual is diagnosed with a pervasivedevelopment disorder (PDD); and (d) administering a pharmaceuticalcomposition comprising digestive enzymes, wherein said pancreaticenzymes comprise amylase, protease and lipase, wherein one or moresymptoms of said PPD are ameliorated.
 96. The method of claim 95,wherein said PDD is selected from the group consisting of Autism,Asperger's, attention deficit disorder (ADD), and attention deficithyperactive disorder (ADHD).
 97. The method of claim 95, wherein saidpancreatic enzymes comprise approximately 12,000 to approximately 24,000U.S.P. units of one or more digestive enzymes.
 98. The method of claim95, wherein said pancreatic enzymes comprise approximately 24,000 toapproximately 36,000 U.S.P. units of one or more digestive enzymes. 99.The method of claim 95, wherein a dose of said pancreatic enzymescomprises from 4000-20,000 U.S.P. units of lipases; 10,000-50,000 U.S.Punits of proteases; 10,000-60,000 U.S.P. units of amylases; 2000-6000U.S.P. units of pancreatin; 2-5 mg of chymotrypsin; or 60-100 mg oftrypsin.